Bone healing
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Transcript of Bone healing
MECHANISMOF
BONE HEALINGDr. Ashraf IbrahimDepartment of OrthopaedicHospital Tuanku Ampuan NajihahKuala Pilah, Negeri Sembilan
Bone histology Component of bone Fracture Fracture healing Types of bone healing Variables influence fracture healing
Cells Osteocytes Osteoblasts Osteoclasts
Extracellular Matrix Organic (35%)
Collagen (type I) 90% Osteocalcin, osteonectin, proteoglycans,
glycosaminoglycans, lipids (ground substance) Inorganic (65%)
Primarily hydroxyapatite Ca5(PO4)3(OH)2
Bone Histology
Cells in Bone
Derived from mesenchymal stem cells
Line the surface of the bone and produce osteoid
Immediate precursor is fibroblast-like preosteoblasts
Picture courtesy Gwen Childs, PhD.
Osteoblasts surrounded by bone matrix trapped in lacunae
Function poorly understood regulating bone metabolism
in response to stress and strain
Picture courtesy Gwen Childs, PhD.
Osteocyte lacunae are connected by canaliculi Osteocytes are interconnected by long cell processes
that project through the canaliculi Preosteoblasts also have connections via canaliculi with
the osteocytes Network probably facilitates response of bone to
mechanical and chemical factors
Derived from hematopoietic stem cells (monocyte precursor cells)
Multinucleated cells whose function is bone resorption
Reside in bone resorption pits (Howship’s lacunae)
Parathyroid hormone stimulates receptors on osteoblasts that activate osteoclastic bone resorption
Picture courtesy Gwen Childs, PhD.
Cortex
Periosteum
Bone marrow
Soft tissue
Bone Histology
Thin Section of Compact Bone
Bone Histology
Periosteum & Endosteum
Structure & Composition
Bone consists of mesenchymal cells imbedded within abundant extra cellular matrix Bone matrix contains mineral gives tissue great strength & stiffness in compression and bending Organic component primary type I collagen great strength in tension
Nerves Lymphatics
BONE
BONE
Two forms of bone tissue
Cortical or compact bone Cancellous or trabecular bone
Two types of bone (mechanical & biological properties)
Woven or immature bone Lamellar or mature bone
Lamellar Bone Orderly cellular distribution
Collagen fibers arranged in parallel layers
Normal adult bone Woven Bone or immature bone (non-
lamellar) Randomly oriented collagen
fibers In adults, seen at sites of
fracture healing, tendon or ligament attachment and in pathological conditions.
Cortical bone Comprised of osteons
(Haversian systems) runs longitudinally
Osteons communicate with medullary cavity by Volkmann’s canals that run horizontally
Picture courtesy Gwen Childs, PhD.
osteon
Haversian canal
osteocyte
Volkmann’s canal
Coarse with random orientation
Weaker than lamellar bone
Normally remodeled to lamellar bone
Figure from Rockwood and Green’s: Fractures in Adults, 4th ed
More rapid rate of deposition & resorption Irregular woven pattern of matrix collagen fibril Four times the number of osteocyte per unit volume Irregular pattern of matrix mineralization
Less stiff & more easily deformed
Potential of mesenchymal cells to deferrentiate
Fracture is a break in the structural continuity of bone .
It may be a crack , a crumpling or a splintering of the cortex.
ON BASIS OF ETIOLOGY - Traumatic fracture - pathologic fractures due to some
diseases - stress fracture ON BASIS OF DISPLACEMEMT - undisplaced - displaced translation ( shift ) angulation ( tilt ) rotation ( twist )
ON BASIS OF RELATIONSHIP WITH EXTERNAL ENVIRONMENT simple / closed fracture open fracture
ON BASIS OF PATTERN Transverse Oblique Spiral Comminuted Segmental
Adequate blood supply Adequate mechanical
stability
FRACTURE HEALING
Sequence of fracture healing
Inflammation Repair Remodeling
Introduction Fracture healing is a complex process that
requires the recruitment of appropriate cells (fibroblasts, macrophages, chondroblasts, osteoblasts, osteoclasts) and the subsequent expression of the appropriate genes (genes that control matrix production and organization, growth factors, transcription factors) at the right time and in the right anatomical location
In 1975, Cruess and Dumont proposed that fracture healing may be considered to consist of three overlapping phases: an inflammatory phase, a reparative phase, and a remodeling phase
In 1989, FROST proposed the stages of fracture healing
five stages. stage of haematoma stage of granulation tissue stage of callus stage of modelling stage of remodelling
Inflammation stage of haematoma
formation Repair stage of granulation
tissue stage of callus formation Remodelling
Stages of Fracture Healing
The inflammatory phase peaks within 48 hours and is quite diminished by 1 week after fracture.
The reparative phase becomes activated within the first few days after fracture and persists for 2-3 months.
The remodelling phase lasts for many years
inflammatory phase is identical to the typical inflammatory response of most tissues to traumatic injury.
Vasodilation and hyperemia, presumably mediated by histamines, prostaglandins, and various cytokines, accompany invasion of the injury site by neutrophils, basophils, and phagocytes that participate in clearing away necrotic debris.
Disruption of blood vessels in the bone, marrow, periosteum, and surrounding tissue disruption at the time of injury results in the extravasation of blood at the fracture site and the formation of a hematoma
Local vessels thrombose causing bony necrosis at the edges of the fracture
Increased capillary permeability results in a local inflammatory milieu Osteoinductive growth factors stimulate the proliferation
and differentiation of mesenchymal stem cells
The reparative phase, which usually begins 4 or 5 days after injury, is characterized by the invasion of pluripotential mesenchymal cells, which differentiate into fibroblasts, chondroblasts, and osteoblasts and form a soft primary fracture callus.
Proliferation of blood vessels (angiogenesis) within the periosteal tissues and marrow space helps route the appropriate cells to the fracture site and contributes to the formation of a bed of granulation tissue.
Mesenchymal cells at the fracture site proliferate differentiate and produce the fracture callus
Two types of callus : Primary callus or Soft callus – forms in the
central region in which there is relatively low oxygen tension
The primary callus may consist of cartilage, fibrous tissue, osteoid, woven bone, and vessels.
If the primary callus is successful, healing progresses to the stage of bridging
callus or hard callus. Hard callus – formed at the periphery of the
callus by intermembranous bone formation
Periosteal callus forms along the periphery of the fracture site Intramembranous ossification initiated
by preosteoblasts Intramedullary callus forms in the
center of the fracture site Endochondral ossification at the site
of the fracture hematoma Chemical and mechanical factors
stimulate callus formation and mineralization
Figure from Brighton, et al, JBJS-A, 1991.
The biochemical composition of the fracture callus matrix changes as repair progresses.
The cells replace the fibrin clot with a loose fibrous matrix containing glycosaminoglycans, proteoglycans, and types I and III collagen
In many regions they convert this tissue to more dense fibrocartilage or hyaline-like cartilage.
With formation of hyaline-like cartilage, type II collagen, cartilage-specific proteoglycan and link protein content increase.
Woven bone is gradually converted to lamellar bone
Medullary cavity is reconstituted Stability of the fracture fragments progressively
increases . eventually clinical union occurs that is, the
fracture site becomes stable and pain-free. Radiographic union occurs when plain
radiographs show bone trabeculae or cortical bone crossing the fracture site, and often occurs later than clinical union .
Despite successful fracture healing, the bone density of the involved limb may be decreased for years
Fracture HealingInflammation
Fracture damages the bone, blood vessels, bone matrix and surrounding soft tissue
Haematoma Inflammatory mediators
-Dilatation blood vessel- Plasma exudate- inflammatory cells- PMN lecocytes- Macrophages- Lymphocytes
Release byplatelets inj.cells
FRACTURE HEALING
Inflammation
MacrophageDegranulating platelets release
- Cytokines (PDGF, TGF ß )- Interleukin 1 & 6- Prostaglandin E2 (PGE2)
Initiation of the repair process
FRACTURE HEALINGINFLAMMATION
Inflammatory Necrosis Tissue and Exudate Resorbed
Fibroplasty & Chondrocytes Appears
Produce new matrix(The fracture callus)
BONE HEALING
REPAIR
Growth factors Fibroblast Growth factor Angiogenesis Osteoclast Osteoblast Bone formation Mesenchymal cells Hard callus intramembranous bone Soft callus endochondral ossification Fracture callus matrix glycosaminoglycans, proteoglycans and collagen type I & III
BONE HEALING
REPAIR
BONE HEALING
Remodelling
Replacement of woven bone by lamellar bone Resorption of unneeded callus mechanical Stability
BONE HEALINGREMODELING
Remodeling of bone trabecula
Accretion and remodeling of bone
BONE HEALING
Fracture healing with rigid stabilization
* Healing with primary bone healing mechanism Gap healing Haversian remodeling
Osteoclast resorb fracture line deposition osteoblast
Blood vessels formation
The new bone matrix + osteocytes form new Haversian Systems or primary osteons
Bone Healing
Direct bone formation in stabilized gap bone
Courtesy AO Risert laboratory
Direct (primary) bone healing Indirect (secondary) bone healing
Mechanism of bone healing seen when there is no motion at the fracture site (i.e. absolute stability)
Does not involve formation of fracture callus
Osteoblasts originate from endothelial and perivascular cells
Contact Healing Direct contact between the fracture ends
allows healing to be with lamellar bone immediately
Gap Healing Gaps less than 200-500 microns are primarily
filled with woven bone that is subsequently remodeled into lamellar bone
Larger gaps are healed by indirect bone healing (partially filled with fibrous tissue that undergoes secondary ossification)
Figure from http://www.vetmed.ufl.edu/sacs/notes
Mechanism for healing in fractures that have some motion, but not enough to disrupt the healing process.
Bridging periosteal (soft) callus and medullary (hard) callus re-establish structural continuity
Callus subsequently undergoes endochondral ossification
Process fairly rapid - weeks
BONE HEALING
Variables Influence Fracture Healing
INJURY VARIABLES
* Open Fractures
Impeding or preventing formation # Hematoma Delaying formation repair tissue Risk of infection
* Severity of Injury
Retard fracture healing
* Intra articular fractures
If the alignment & congruity joint surface is not restored Delayed healing or non union Joint stiffness
* Segmental fractures
* Soft tissue interposition
* Damage to the blood supply
INJURY VARIABLES
BONE HEALING
BONE HEALING
Variables Influence Fracture Healing
Patient Variables
* Age* Nutrition
Healing process needs
- Energy- Proteins & carbohydrates
- Corticosteroid ( )- Growth hormone- Thyroid hormone- Calcitonin- Insulin- Anabolic steroids- DM- Hypervitaminosis D- Rickets
* Systemic hormones
* Nicotine
- Inhibit fracture healing ( Vascularization?)
Rate fracture healing
Frame healing
BONE HEALING
Patient variables
BONE HEALINGVariables Influence Fracture Healing
Tissue Variables* Cancellous or cortical bones* Bone necrosis* Bone disease
Pathologic fracture Osteoprosis Osteomalacia Primary malignant bone tumors Metastatic bone tumors Benign bone tumors Bone cysts Osteogenesis imperfecta Paget’s disease Fibrous dysplacia Hyperparathyroidism
* Infection
BONE HEALING
Variables Influence Fracture Healing
Treatment Variables
• Apposition of fracture fragments• Loading & micromotion
Loading a fracture site stimulates bone formation Micromotion promotes fracture healing
• Fracture stabilization
-Traction- Cast Imm- Ext.Fixation- Int.Fixation
Facilitate fracture healing byPreventing repeated disruption ofRepair tissue
Potential disadvantage of int.fixation :
Surgical exposure disrupted hematoma, blood supply Risk of infection Rigid fixation alter fracture remodeling, bone density
BONE HEALING
Treatment Variables
BONE HEALING
Promote Fracture Healing
Bone Grafting • Autografts• Freezing & Freez drying allografts
Bone transport callus distraction Electrical fields
•Stimulate cell proliferation• Promote bone formation
Ultra Sound
Aggrecan gene expression Concentration intracellular Ca in callus chondrocyte
Demineralized bone matrix, growth factors & antologus bone narrow
Apley’s System of Orthopaedic and Fractures, 9th edition
eMedicine, Bone remodelling www.ncbi.nlm.nih.gov/pmc/articles/
PMC3109437/